Although in vivo studies have indicated a direct stimulatory effect of androgens on hematopoietic stem cells and early erythroblast descendants of these cells, there is virtually no information on the molecular events that underlie specific interaction of these steroids with erythropoietic tissues. The proposed project is a study of such events in the erythropoietic mouse spleen formed in response to a phenylhydrazine-induced hemolytic anemia. This organ undergoes an orderly sequence of development with a predominance of nucleated cells present as erythroblasts. Prior studies in our laboratory have indicated a stereospecific uptake of testosterone restricted to the early phase of erythropoietic spleen development. Stereospecific cytosol receptor(s) for testosterone have been identified in extracts of early phase spleens. The projected study will undertake the purification and characterization of these cytosol receptors and their subsequent role as steroid-receptor complexes in transport to intranuclear structures. The molecular specificities of the androgen ligands in binding will be determined in order to select one or more of these steroids for the predominance of its erythropoietic effect as opposed to virilization, etc. Such a development should be helpful in adding to the therapy of refractory anemias.